ACTA BIOLOGICA CRACOVIENSIA

16 TH INTERNATIONAL SYMPOSIUM ON CAROTENOIDS
sumption of fruits and vegetables (Khachik et al., 2006). Among
these are hydroxycarotenoids: (3R,3'R,6'R)-lutein {1}, (3R,3'R)zeaxanthin
{2}, (3R,6'R)-α-cryptoxanthin {3}, and (3R)-β-cryptoxanthin
{4}. In addition, several dehydration products of {1} have
also been identified in human serum, these are: (3R,6'R)-3hydroxy-3',4'-didehydro-β,γ-carotene
{5} (3R,6'R)-3-hydroxy-2',3'didehydro-β,ε-carotene
{6}, and (3R)-3-hydroxy-3',4'-didehydroβ,
β-carotene {7}. Hydroxycarotenoids {1} and {2} appear to
undergo extensive metabolism to several ketocarotenoids by a
series of oxidation-reduction and double bond isomerization
reactions. For example, (3R,3'S,6'R)-lutein (3'-epilutein, {8}) and
(3R,3'S;meso)-zeaxanthin {9} are among the metabolites of {1}
and/or {2} in human serum and ocular tissues that are formed by
such reactions. The lack of commercial availability of some of
these non-vitamin A active dietary carotenoids has limited the
investigation of their metabolism and their biological activity.
While the total synthesis of {1} and four of its stereoisomers has
been reported (Khachik and Chang, 2009), the isolation of this
carotenoid from marigold flowers (Tagetes erecta) on industrial
scale has proven to be the most viable and inexpensive route to
this carotenoid. In addition, 1 with stereocenters at 3,3',6'-positions
serves as an excellent precursor in the partial synthesis of
hydroxycarotenoids with ε–and β-end groups. Therefore, several
semi-synthetic processes have been developed that separately
transform {1} into {4} via {7} as well as {1} into {8}. While {8}
is converted into {2} by base-catalyzed isomerization, {7} is
transformed into {2} and its (3R,3'S;meso)-stereoisomer {9} by
regioselective hydroboration followed by enzyme-mediated acylation
that allows the separation of these carotenoids (Khachik et
al., 2007). In another process, regioselective allylic deoxygenation
of {1} afforded {3} that has been successfully transformed into
(6'R)-α-cryptoxanthin {10}. The preparation and resolution of
(3R)-3-hydroxy-β-ionone and its (3S)-stereoisomer that are
important precursors in the total synthesis of {2} and {4} and
their stereoisomers will be described.
REFERENCES
KHACHIK F. 2006. Distribution and metabolism of dietary carotenoids in
humans as a criterion for development of nutritional supplements.
Pure Appl. Chem. 78: 1551-57.
KHACHIK F and CHANG AN. 2009. Total synthesis of (3R,32R,62R)-lutein
and its stereoisomers. J. Org. Chem. 74: 3875-3885.
KHACHIK F, CHANG AN, GANA A, MAZZOLA E. 2007. Partial synthesis of
(3R,6'R)-α-cryptoxanthin and (3R)-β-cryptoxanthin from
(3R,3'R,6'R)-lutein. J. Nat. Prod. 70: 220-226.
Isomers and apo-carotenoids in biological
matrices
Steven J. Schwartz
Department of Food Science and Interdisciplinary Graduate
Program in Nutrition, The Ohio State University, Columbus, Ohio,
USA 43210. Schwartz.177@osu.edu
Conversion of carotenoids to geometrical (E, Z) isomers and
more recently to apo-carotenoids and apo-lycopenoids has been
the subject of various investigations. Analysis of carotenoids has
revealed the formation of several geometrical isomers created
during thermal processing of carotenoid rich plant foods.
However, the susceptibility of carotenoids to isomerization
appears to be matrix dependent and favored when carotenoids
are associated with lipid. Previous reports have demonstrated
that cis isomers of beta-carotene are not readily absorbed in
humans. In contrast, lycopene isomers are absorbed and in-vivo
isomerization reactions proceed readily following uptake. Data
from clinical trials in humans show that relatively high percentage
of lycopene isomers (approx. 60-80%) are found circulating in
SESSION 3
blood plasma and deposited in tissues. However, the mechanism
for in-vivo conversion remains to be elucidated but appears to
proceed to equilibrium during absorption and circulation within
the bloodstream at physiological temperatures. Although oxidative
eccentric cleavage mechanisms of carotenoids have been well
documented, few reports have unequivocally identified the in-vivo
apo-carotenoid and apo-lycopenoid metabolic products. Our laboratory
has developed highly selective and sensitive LC MS/MS
methodology to analyze these compounds in foods and biological
tissues. In collaboration with other researchers at the Ohio State
University several eccentric cleavage products have been identified
by comparison to synthesized authentic compounds and
their potential biological activity demonstrated.
Superlative carotenoids: the shortest, the
longest, the cleanest, the fattiest, the most
precious, the most water-soluble, the ultimate
antireductant, the smallest aggregated and the
best DNA-carrier carotenoid
Hans-Richard Sliwka
Department of Chemistry, Realfagbygg, Norwegian University of
Science and Technology, 7491 Trondheim, Norway,
hrs@nvg.ntnu.no
Syntheses to carotenoids have long been the ultimate goal for
carotenoid chemists. Syntheses with carotenoids are still hampered
by the popular opinion that carotenoids are too sensitive
for chemical manipulations. However, some of the commercially
available carotenoids bear reactive functional groups such as
-COOR, -CHO, -CO, -OH. A carotenoid with COOH can, therefore,
be considered a highly unsaturated fatty acid, which can form
highly unsaturated fatty acid alkali salts or inherently colored
soaps. Highly unsaturated carotenoic acids may also replace saturated
fatty acids in glycerolipids and phospholipids, which
result in the formation of highly unsaturated fats. Carotenoid
acids and carotenols can be esterified with hydrophilic substituents
inducing water-solubility or water-dispersibility to the
otherwise hydrophobic carotenoids. The C=O group in ketocarotenoids
can easily be replaced with C=S, which is highly
absorptive on Ag or Au for monolayer assembling. The CHO
group invites to carotenoid prolongation in Wittig reactions.
Other reactions with carotenoids can soon reach the reasonable
limit in yield and stability. Still, low yields in a one-step synthesis
may counterbalance higher yields in multistep syntheses.
One positive effect of carotenoids cannot be overestimated:
carotenoids introduce color to otherwise sallow compounds providing
instant visual confirmation of product formation; the
carotenoid color facilitates work-up procedures and allows chiroptical
detection of typically "invisible" molecules, e.g. carotenoid
glycerolipid enantiomers give CD spectra.
The presentation illustrates the use of carotenoids in synthesis,
highlights some unique results and exemplifies the use of
carotenoid-modified compounds in spectroscopy, as
pharmaphores, and in the study of aggregation and surface properties.
Right and proper acknowledgements will be given to the
many collaborators participating in this work.
50 ACTA BIOLOGICA CRACOVIENSIA Series Botanica